Report from Stanford Event: Human Germline Modification: Medicine, Science, Ethics, & Law

Greely_HankLast Thursday I participated in a meeting at Stanford Law School on human germline genetic modification hosted by Hank Greely (pictured at left), Professor of Law and Genetics at Stanford.

The meeting was entitled, “Human Germline Modification: Medicine, Science, Ethics, and Law”. The panel included in addition to Hank and me, the following speakers: Marcy Darnovsky, Executive Director of the Center for Genetics and Society (CGS); Christopher (Chris) Thomas Scott, Stanford Center for Biomedical Ethics, and Lynn M. Westphal, Professor of Obstetrics and Gynecology, Stanford University Medical School.

We each spoke for about 10-15 minutes, followed by a rousing discussion with the audience of about 50 people and between us panelists. The audience asked great questions. A video of the meeting is now available (below).MarcyDarnovsky_2012

I’m just going to blog here focusing on my impressions of the meeting and I’m in no way speaking for the other panelists. I hope that if they have other ideas about how the meeting went or their own views in response to my post that they will weigh in as well. I want to thank Hank for the invitation to participate and the other panelists for a great meeting. I came away having learned some important new things and with a broader perspective on human embryo editing.

Part of what made this meeting so interesting to me was the wide range of views on human  modification of the participants and the audience. My sense was that Marcy (picture above right) has the strongest concerns about heritable human genetic modification amongst us speakers. CGS, her organization, just last week I think outlined 7 reasons on their website to “just say no to human genetic modification” and she articulated some of her concerns at the meeting. I share some of her concerns, but don’t feel quite as strongly about human embryo editing and I favor allowing in vitro research under some conditions. Marcy and I also disagreed on whether human germline modification is inevitable. I think it is, while she doesn’t. I got the sense that she is concerned that talk of inevitability could discourage efforts to restrict the technology.

Christopher Thomas ScottOn the other side, it seemed to me that Lynn was perhaps more open to the possibility of modification being used in the future if deemed safe, particularly if it could help infertile couples have their own genetically related children. I found it very interesting to hear about Lynn’s experience as a physician on the medical frontline interacting with couples dealing with infertility or genetic problems including mitochondrial disorders. In communicating with Chris afterwards he mentioned that he was struck by the way in which Lynn indicated that there could well be pressures from patients for therapeutic embryo editing. My sense too was that Lynn wouldn’t be shocked if clinical application of human editing technology was eventually attempted by fertility doctors.

Hank and Chris seemed relatively less concerned than Marcy about human germline modification overall and more confident that it can be regulated appropriately. Chris, pictured above left, also did an excellent job explaining the science behind CRISPR and highlighting what makes it so important and unusual compared to past technologies. Like Chris, I’m more inclined to let some in vitro research (conduced with appropriate ethical and institutional approval and oversight) on human germline modification proceed (see my ABCD plan) and I got the sense that is Hank’s view as well. But there should be a compelling, logical rationale for doing the work in embryos rather than cells.

My impression was that we all could agree that for dealing with most genetic disorders preimplantation genetic diagnosis (PGD) would be far preferable to trying to make a genetic correction in a human embryo.

Hank pointed out three scenarios where PGD likely wouldn’t work to correct a problematic genetic situation and hence gene editing could be needed:

  • 1. Dominant genetic disease with one parent being homozygous
  • 2. Both parents have some kind of mutation in the same gene
  • 3. Certain kinds of mitochondrial disease

I know a lot of people have been trying to think through possible situations where gene editing might be needed and PGD wouldn’t solve a particular problem so it was great to hear Hank articulate how these three fit into that category. Hank and others mentioned how these would be very rare circumstances, but not entirely unheard of so in principle at least there could be a unique role for editing over PGD in humans if proven safe and effective. It is also possible that some rare sex-linked disorders could not be resolvable by PGD.Lynn M. Westphal

Lynn, pictured at right, also added in importantly I thought that for some couples there are so few embryos that PGD is unlikely to work to find one lacking a mutation. I wondered aloud: how many human embryos might take to get CRISPR to work for editing too? It might take quite a few.

We had a good discussion of the example of potential genetic modification of a human embryo for the correction of a BRCA1 breast/ovarian cancer-associated gene mutation. It was pointed out by several that this mutation is not a “causal” mutation in the sense of always leading to disease, but only a predisposition to disease.

If it were decided that human editing for BRCA1 is acceptable, then I suggested that other weaker genetic predispositions might be considered legitimate as well. This could create somewhat of a gray area whereby human genetic modification becomes considered appropriate simply for predispositions including some that might be viewed as only moderate such as say a 30% increased risk of Alzheimer’s or cognitive disability in children. There’s could end up being a bit of blurring there where we could see enhancements occurring too. I felt that there wouldn’t always been a clear, bright line between medical use and enhancements with human germline editing.

I thought Chris raised some great points about issues related to scientific publishing and human germline modification. Why did the journal Protein & Cell, which published the first human embryo editing paper just a few weeks ago, only come out with an editorial days later explaining why they decided to publish the paper rather than having an editorial accompanying the actual research article? To me it definitely seemed reactionary and in response to critical questions raised about the embryo editing paper rather than with forethought about how it would be important to place this publication in an appropriate context right from the beginning.

Chris also pointed out that a key question still open for debate is whether this embryo editing paper should have been published at all. To me it seems like not a whole lot was gained specifically by doing this CRISPR’ing in actual human embryos rather than cell lines.

Some of the questions from the audience included asking about how human modification might change the relationship between parents and children as well as how commercialization could impact the evolution of human editing via CRISPR-Cas9. Another point that came up during the discussion was the concern over potential strong negative impact of gene editing of animals (not humans) either for us as novelty pets or in the wild.

Overall it was a wonderful, very useful meeting that advanced the discussion of human modification forward. I hope that these types of meetings continue and that there is more discussion of this kind involving diverse stakeholders as well as the public.